Longevity in obese and lean male and female rats of the Zucker strain: prevention of hyperphagia

Johnson, Patricia R.; Stern, Judith S.; Horwitz, Barbara A; Harris, Robert S.; Greene, Stephanie F.

doi:10.1093/ajcn/66.4.890

Cited by 75 publications

(49 citation statements)

References 38 publications

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“…24 In the present study, however, SBP was higher in DS/obese rats than in DS/lean rats and in Zucker fatty rats at 11 weeks and thereafter, suggesting that the presence of the fa allele of Lepr on the DahlS background is associated with increased salt sensitivity of blood pressure, which may contribute to the development of cardiovascular complications and premature death within shorter period than in Zucker fatty rats. 9,25 The arterial pressure control mechanism of diuresis and natriuresis appears to be shifted toward higher blood pressure levels in obese individuals. 26 The elevation of SBP in DS/ obese rats was also accompanied by the increases in both homeostasis model assessment-insulin resistance and cardiac inflammatory responses, consistent with the concept that insulin resistance and inflammation may give rise to an altered profile of vascular function and thereby lead to hypertension.…”

Section: Discussionmentioning

confidence: 99%

Cardiac remodeling and diastolic dysfunction in DahlS.Z-Leprfa/Leprfa rats: a new animal model of metabolic syndrome

et al. 2011

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We recently characterized male DahlS.Z-Lepr fa /Lepr fa (Dahl salt-sensitive (DS)/obese) rats, which were established from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome (MetS). We have now investigated cardiac pathophysiology and metabolic changes in female DS/obese rats in comparison with homozygous lean female littermates (DahlS.Z-Lepr + /Lepr + , or DS/lean, rats). Animals were maintained on a normal diet and were subjected to echocardiography followed by various pathological analyses at 15 weeks of age. Systolic blood pressure was significantly higher in female DS/obese rats than in DS/lean females at 12 weeks of age and thereafter. The survival rate of DS/obese rats was significantly lower than that of DS/lean rats at 15 weeks. Body weight, as well as visceral and subcutaneous fat mass were significantly increased in DS/obese rats, which also manifested left ventricular (LV) diastolic dysfunction and marked LV hypertrophy and fibrosis. In addition, myocardial oxidative stress and inflammation were increased in DS/obese rats compared with DS/lean rats. Serum insulin and triglyceride levels as well as the ratio of low-density lipoprotein-to high-density lipoprotein-cholesterol levels were markedly elevated in DS/obese rats, whereas fasting serum glucose concentrations were similar in the two rat strains. The phenotype of female DS/obese rats is similar to that of MetS in humans. These animals also develop salt-sensitive hypertension and LV diastolic dysfunction as well as LV hypertrophy and fibrosis, and these changes are associated with increased cardiac oxidative stress and inflammation. Keywords: cardiac hypertrophy; diastolic dysfunction; metabolic syndrome; myocardial fibrosis; salt-sensitive hypertension INTRODUCTION Metabolic syndrome (MetS), a complex of highly debilitating disorders including hypertension, diabetes mellitus and dyslipidemia, is associated with the development of visceral obesity. 1 Adipocytes in visceral fat of obese humans secrete a variety of biological agents that are known as adipocytokines and include proinflammatory cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-6 as well as angiotensinogen and leptin. 2 Recent studies have revealed intricate interactions among adipocytes, the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) that contribute to the disturbed metabolic state associated with obesity. 3 Indeed, adipose tissue is thought to have an important role in the development of both hypertension and other complications related to insulin resistance. Activation of the RAAS and associated oxidative stress can result in mitochondrial abnormalities, altered bioenergetics and the accumulation of lipids in the heart, and thereby increase susceptibility to metabolic cardiomyopathy. 4

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Section: Discussionmentioning

confidence: 99%

Cardiac remodeling and diastolic dysfunction in DahlS.Z-Leprfa/Leprfa rats: a new animal model of metabolic syndrome

et al. 2011

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“…All groups were fed a soy protein-based diet (20% w/w), shown to minimize diet-induced nephropathy and previously used in our work (3,10). The diet of the PF rats was vitamin-enriched relative to that of animals fed ad libitum during the period of restriction, with the weight of the vitamin mix being increased from 2.0% to 3.33% of the diet.…”

Section: Dietmentioning

confidence: 99%

“…Hence, animal models of obesity in which renal disease develops are highly relevant to understanding the pathophysiology of the morbidity associated with obesity. In obese (fa/fa) Zucker rats (OZRs), an animal model of hyperphagia, obesity, and hyperlipidemia, ESRD secondary to glomerular sclerosis is a primary cause of death and can be attenuated by eliminating hyperphagia (3,4).…”

Section: Introductionmentioning

confidence: 99%

Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

et al. 2001

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Objective: We sought to determine whether prevention of overeating would block the very earliest manifestations of renal injury in young obese Zucker rats (OZRs). Research Methods and Procedures: Three groups of rats were studied, obese (fa/fa) Zucker rats and lean (Fa/Fa). Zucker controls were allowed to feed ad libitum, whereas a group of obese (fa/fa) Zucker rats was pair-fed to the lean group. Urine albumin and serum lipids were studied weekly from 6 to 10 weeks of age. Renal pathology and renal glomerular gene expression were examined when the rats were killed at 10 weeks of age. Results: Obese rats fed ad libitum developed significant albuminuria by 6 weeks of age, increasing at each subsequent time-point. This increase was completely blocked by pair-feeding. Serum triglycerides were significantly increased in obese rats fed ad libitum vs. the other groups. Urine albumin correlated significantly with both body weight and serum triglyceride level. Renal histopathology was normal in all groups. Analysis of gene expression of glomerular proteins by reverse transcriptase-polymerase chain reaction revealed that pair-feeding attenuated the increased expression of glomerular desmin, fibronectin, and the 92-kDa collagenase that was seen in obese animals fed ad libitum. Discussion: Prevention of overeating in young OZR normalizes albuminuria and attenuates the pathogenic alterations in glomerular gene expression seen at the initiation of renal disease in obese animals allowed to feed ad libitum. This model may be relevant for studying the early endorgan effects of obesity.

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“…In addition, it has been previously demonstrated in the literature that leptin may promote renal injury through binding to the short leptin receptor, which is expressed more abundantly in the kidney than in the brain (31). Obese Zucker rats are also a good model for studying obesity-related renal disease because these animals also develop glomerular hypertension, glomerular hypertrophy, proteinuria, and focal segmental glomerulosclerosis (5,10,14,30). In fact, the cause of death in these rats is often due to end-stage renal disease (14).…”

mentioning

confidence: 99%

Renoprotective mechanisms of soy protein intake in the obese Zucker rat

Trujillo¹,

Cruz²,

Tovar³

et al. 2008

American Journal of Physiology-Renal Physiology

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We previously showed that long-term consumption of a soy protein diet (SoyP) reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO 2 and NO 3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may contribute to the renal progression observed in this model. In addition, there is compelling evidence that hyperleptinemia produced deleterious effects on the kidney through its interaction with the short leptin receptor (ObRa). This study was designed to evaluate the contribution of the NO/endothelial NO synthase (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the other half with a 20% casein protein diet (CasP) over the course of 160 days. eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-␤, and kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were measured. Renal injury observed in ObeseZ rats fed with CasP was not associated with changes in eNOS expression or phosphorylation. However, this group did present with increased rLPO, reduced catalase activity, and upregulation of ObRa, TGF-␤1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase activity. These findings were associated with a significant reduction of ObRa, TGF-␤1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative stress, together with a significant reduction in ObRa and TGF-␤ expression. oxidative stress; nitric oxide; endothelial nitric oxide synthase phosphorylation; short leptin receptor

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Longevity in obese and lean male and female rats of the Zucker strain: prevention of hyperphagia

Cited by 75 publications

References 38 publications

Cardiac remodeling and diastolic dysfunction in DahlS.Z-Leprfa/Leprfa rats: a new animal model of metabolic syndrome

Cardiac remodeling and diastolic dysfunction in DahlS.Z-Leprfa/Leprfa rats: a new animal model of metabolic syndrome

Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

Renoprotective mechanisms of soy protein intake in the obese Zucker rat

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